The biologic activity of a potent analogue of gonadotropin-releasing hormone in normal and hypogonadotropic men.

We studied the biologic activity of a long-acting analogue of luteinizing hormone-releasing hormone, D-Trp6-Pro9-NEt-LHRH (LHRHa), in five normal men and four hypogonadotropic men previously unresponsive to natural LHRH. All subjects responded to LHRAa, but there were quantitative and qualitative differences between the normal and hypogonadotropic men. Normal men showed a linear dose-response relation, endogenous gonadal steroid secretion, and an adult pattern of gonadotropin secretion characterized by a high ratio of luteinizing hormone (LH) to follicle-stimulating hormone (FSH). Hypogonadotropic men had improving pituitary responses to each dose of LHRHa (priming response), no demonstrable gonadal steroid secretion, and a prepubertal pattern of gonadotropin release characterized by reversal of the normal ratio of LH to FSH. When compared with native LHRH, LHRHa had an augmented ability to discharge gonadotropins acutely and to sustain their release in normal and hypogonadotropic men.